Birth of monozygotic dichorionic twins after a single blastocyst embryo transfer: a case report of genetic determination of zygosity.

Objective: To report a case of monozygotic dichorionic (DC) twins after a single cryopreserved blastocyst embryo transfer followed by genetic determination of zygosity postpartum. Design: Case report. Setting: University hospital. Patients: A 26-year-old woman with polycystic ovary syndrome and her 36-year-old male partner with severe oligozoospermia, resulting in a 1.5-year history of primary infertility. Interventions: Controlled ovarian stimulation and intracytoplasmic sperm injection treatment with single cryopreserved embryo transfer at blastocyst stage. Main Outcome Measures: Ultrasound images of the fetuses and short tandem repeat genotyping postpartum. Results: A DC twin pregnancy following a single cryopreserved blastocyst embryo transfer was confirmed at the first trimester screening. Confirmatory testing performed postpartum included short tandem repeat analysis determining monozygosity and pathology examination reporting DC placental configuration. Conclusions: Dichorionic monozygotic twins are thought to arise from the splitting of an embryo before the blastocyst stage. This case suggests that placental configuration of monozygotic twins may not strictly depend on timing of embryo division. Genetic analysis is the only tool to confirm the zygosity.

Impact of Thyroid Function on Pregnancy and Neonatal Outcome in Women with and without PCOS.

Background: Women with polycystic ovary syndrome (PCOS) are more prone to autoimmune thyroiditis, and both disorders lead to subfertility and pregnancy-related complications. The aim of this study was to investigate whether mothers with and without PCOS and their offspring have comparable thyroid parameters at term and how thyroid parameters are associated with perinatal outcome in this population. Methods: This cross-sectional observational study was performed in a single academic tertiary hospital in Austria. Seventy-nine pregnant women with PCOS and 354 pregnant women without PCOS were included. Blood samples were taken from the mother and cord blood at birth. Primary outcome parameters were maternal and neonatal thyroid parameters at delivery. Secondary outcome parameters were the composite complication rate per woman and per neonate. Results: Thyroid dysfunction was more prevalent among PCOS women (p < 0.001). At time of birth, free triiodothyronine (fT3) levels were significantly lower in PCOS than in non-PCOS women (p = 0.005). PCOS women and their neonates had significantly higher thyreoperoxidase antibody (TPO-AB) levels (p = 0.001). Women with elevated TPO-AB had a significantly higher prevalence of hypothyroidism (p < 0.001). There was a significant positive correlation between maternal and neonatal free thyroxine, fT3 and TPO-AB levels. There were no significant differences in thyroid parameters between women or neonates with or without complications. Conclusions: Our results demonstrate a higher prevalence of thyroid dysfunction and autoimmunity in PCOS women, supporting a common etiology of both disorders. We were not able to show an association between complication rate and thyroid parameters.

European Expert Consensus on Practical Management of Specific Aspects of Parathyroid Disorders in Adults and in Pregnancy: Recommendations of the ESE Educational Program of Parathyroid Disorders.

This European expert consensus statement provides recommendations for the diagnosis and management of primary hyperparathyroidism (PHPT), chronic hypoparathyroidism in adults (HypoPT), and parathyroid disorders in relation to pregnancy and lactation. Specified areas of interest and unmet needs identified by experts at the second ESE Educational Program of Parathyroid Disorders (PARAT) in 2019, were discussed during two virtual workshops in 2021, and subsequently developed by working groups with interest in the specified areas. PHPT is a common endocrine disease. However, its differential diagnosing to familial hypocalciuric hypercalcemia (FHH), the definition and clinical course of normocalcemic PHPT, and the optimal management of its recurrence after surgery represent areas of uncertainty requiring clarifications. HypoPT is an orphan disease characterized by low calcium concentrations due to insufficient PTH secretion, most often secondary to neck surgery. Prevention and prediction of surgical injury to the parathyroid glands are essential to limit the disease-related burden. Long-term treatment modalities including the place for PTH replacement therapy and the optimal biochemical monitoring and imaging surveillance for complications to treatment in chronic HypoPT, need to be refined. The physiological changes in calcium metabolism occurring during pregnancy and lactation modify the clinical presentation and management of parathyroid disorders in these periods of life. Modern interdisciplinary approaches to PHPT and HypoPT in pregnant and lactating women and their newborns children are proposed. The recommendations on clinical management presented here will serve as background for further educational material aimed for a broader clinical audience, and were developed with focus on endocrinologists in training.

Recombinant versus bovine hyaluronidase for oocyte denudation before intracytoplasmic sperm injection: a systematic review and meta-analysis.

The removal of cumulus cells in a process called oocyte denudation is required in order to visualise, grade and manipulate the oocytes before injection. The objective of this study was to appraise critically the published randomised controlled trials (RCTs) comparing recombinant hyaluronidase with bovine hyaluronidase for oocyte denudation before intracytoplasmic sperm injection (ICSI). We performed a comprehensive literature search of the standard medical databases in order to identify the RCTs comparing oocyte denudation with recombinant hyaluronidase or bovine hyaluronidase before ICSI. Three RCTs involving 2445 oocytes collected from 200 women were analysed. There was substantial heterogeneity among the included RCTs. A meta-analysis from the available moderate to high quality trials found no statistical difference in terms of fertilisation rate, embryo quality and live birth rate between the use of recombinant or bovine hyaluronidase for oocyte denudation before ICSI.IMPACT STATEMENTWhat is already known on this subject? The removal of cumulus cells in a process called oocyte denudation is required in order to visualise, grade and manipulate the oocytes before injection. The long-established source of hyaluronidase has been represented by bovine testes, but concern has been raised regarding the possible negative effects over the fragile oocytes by mechanisms involving low enzyme purity, variable concentrations, trauma, prolonged exposure and integration of external DNA in the oocyte. Recombinant human hyaluronidase has been proposed as an alternative in order to counteract the possible negative effects of using animal derived products.What do the results of this study add? A meta-analysis from the available moderate to high quality trials found no statistical difference in fertilisation rate, embryo quality and live birth rate between the use of recombinant or bovine hyaluronidase for oocyte denudation before ICSI.What are the implications of these findings or clinical practice and/or further research? Future trials should be powered adequately in order to be able to identify the possible small differences between the study groups and they should be conducted according to the CONSORT guidelines as the absence of blinding for outcome assessors can induce detection bias.

Oxytocin antagonists for assisted reproduction.

BACKGROUND: Embryo transfer (ET) is a crucial step of in vitro fertilisation (IVF) treatment, and involves placing the embryo(s) in the woman's uterus. There is a negative association between endometrial wave-like activity (contractile activities) at the time of ET and clinical pregnancy, but no specific treatment is currently used in clinical practice to counteract their effects. Oxytocin is a hormone produced by the hypothalamus and released by the posterior pituitary. Its main role involves generating uterine contractions during and after childbirth. Atosiban is the best known oxytocin antagonist (and is also a vasopressin antagonist), and it is commonly used to delay premature labour by halting uterine contractions. Other oxytocin antagonists include barusiban, nolasiban, epelsiban, and retosiban. Administration of oxytocin antagonists around the time of ET has been proposed as a means to reduce uterine contractions that may interfere with embryo implantation. The intervention involves administering the medication before, during, or after the ET (or a combination). OBJECTIVES: To evaluate the effectiveness and safety of oxytocin antagonists around the time of ET in women undergoing assisted reproduction. SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility (CGF) Group trials register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, and two trials registers in March 2021; and checked references and contacted study authors and experts in the field to identify additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of the use of oxytocin antagonists for women undergoing ET, compared with the non-use of this intervention, the use of placebo, or the use of another similar drug. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures recommended by Cochrane. Primary review outcomes were live birth and miscarriage; secondary outcomes were clinical pregnancy and other adverse events. MAIN RESULTS: We included nine studies (including one comprising three separate trials, 3733 women analysed in total) investigating the role of three different oxytocin antagonists administered intravenously (atosiban), subcutaneously (barusiban), or orally (nolasiban). We found very low- to high-certainty evidence: the main limitations were serious risk of bias due to poor reporting of study methods, and serious or very serious imprecision. Intravenous atosiban versus normal saline or no intervention We are uncertain of the effect of intravenous atosiban on live birth rate (risk ratio (RR) 1.05, 95% confidence interval (CI) 0.88 to 1.24; 1 RCT, N = 800; low-certainty evidence). In a clinic with a live birth rate of 38% per cycle, the use of intravenous atosiban would be associated with a live birth rate ranging from 33.4% to 47.1%. We are uncertain whether intravenous atosiban influences miscarriage rate (RR 1.08, 95% CI 0.75 to 1.56; 5 RCTs, N = 1424; I² = 0%; very low-certainty evidence). In a clinic with a miscarriage rate of 7.2% per cycle, the use of intravenous atosiban would be associated with a miscarriage rate ranging from 5.4% to 11.2%. Intravenous atosiban may increase clinical pregnancy rate (RR 1.50, 95% CI 1.18 to 1.89; 7 RCTs, N = 1646; I² = 69%; low-certainty evidence), and we are uncertain whether multiple or ectopic pregnancy and other complication rates were influenced by the use of intravenous atosiban (very low-certainty evidence). Subcutaneous barusiban versus placebo One study investigated barusiban, but did not report on live birth or miscarriage. We are uncertain whether subcutaneous barusiban influences clinical pregnancy rate (RR 0.96, 95% CI 0.69 to 1.35; 1 RCT, N = 255; very low-certainty evidence). Trialists reported more mild to moderate injection site reactions with barusiban than with placebo, but there was no difference in severe reactions. They reported no serious drug reactions; and comparable neonatal outcome between groups. Oral nolasiban versus placebo Nolasiban does not increase live birth rate (RR 1.13, 95% CI 0.99 to 1.28; 3 RCTs, N = 1832; I² = 0%; high-certainty evidence). In a clinic with a live birth rate of 33% per cycle, the use of oral nolasiban would be associated with a live birth rate ranging from 32.7% to 42.2%. We are uncertain of the effect of oral nolasiban on miscarriage rate (RR 1.45, 95% CI 0.73 to 2.88; 3 RCTs, N = 1832; I² = 0%; low-certainty evidence). In a clinic with a miscarriage rate of 1.5% per cycle, the use of oral nolasiban would be associated with a miscarriage rate ranging from 1.1% to 4.3%. Oral nolasiban improves clinical pregnancy rate (RR 1.15, 95% CI 1.02 to 1.30; 3 RCTs, N = 1832; I² = 0%; high-certainty evidence), and probably does not increase multiple or ectopic pregnancy, or other complication rates (moderate-certainty evidence). AUTHORS' CONCLUSIONS: We are uncertain whether intravenous atosiban improves pregnancy outcomes for women undergoing assisted reproductive technology. This conclusion is based on currently available data from seven RCTs, which provided very low- to low-certainty evidence across studies. We could draw no clear conclusions about subcutaneous barusiban, based on limited data from one RCT. Further large well-designed RCTs reporting on live births and adverse clinical outcomes are still required to clarify the exact role of atosiban and barusiban before ET. Oral nolasiban appears to improve clinical pregnancy rate but not live birth rate, with an uncertain effect on miscarriage and adverse events. This conclusion is based on a phased study comprising three trials that provided low- to high-certainty evidence. Further large, well-designed RCTs, reporting on live births and adverse clinical outcomes, should focus on identifying the subgroups of women who are likely to benefit from this intervention.

Cardio-pathogenic variants in unexplained intrauterine fetal death: a retrospective pilot study.

To describe the prevalence and spectrum of cardio-pathogenic variants in singleton fetuses after unexplained intrauterine fetal death (IUFD). DNA from post-mortem fibroblastic tissue samples of 16 fetuses after unexplained IUFD was retrieved at two tertiary university hospitals for clinical exome sequencing with subsequent filtering of 122 cardio-specific genes to elucidate underlying cardio-pathogenic variants. In total, we included 12 (75%) male and four (25%) female fetuses who were stillborn at a median gestational age of 34+6 (23+2-40+5) weeks. In two (12.5%) fetuses no cardio-pathogenic variants were found. In 14 (87.5%) fetuses, overall 33 variants were detected in 22 cardio-specific genes, involving 14 (63.63%) genes associated with cardiomyopathy, six (27.27%) arrhythmogenic susceptibility genes and two (9.09%) arrhythmia and cardiomyopathy associated genes. Among the 33 variants, five (15.2%) were classified as likely benign according to the American College of Medical Genetics and Genomics; 28 (84.8%) variants were considered as variants of uncertain significance. Compared to a cohort of explained IUFDs, the cases with and without fetal variants in cardiac genes differed not significantly regarding maternal age, previous history of stillbirth, time of stillbirth or fetal sex. Unexplained stillbirth may be caused by cardio-genetic pathologies, yet a high number of variants of uncertain significance merit a more detailed post-mortem examination including family segregation analysis.

Maternal Angiotensin Increases Placental Leptin in Early Gestation via an Alternative Renin-Angiotensin System Pathway: Suggesting a Link to Preeclampsia.

[Figure: see text].

Effects of Vitamin D Supplementation on Surrogate Markers of Fertility in PCOS Women: A Randomized Controlled Trial.

Vitamin D (VD) might play an important role in polycystic ovary syndrome (PCOS) and female fertility. However, evidence from randomized controlled trials (RCT) is sparse. We examined VD effects on anti-Müllerian hormone (AMH) and other endocrine markers in PCOS and non-PCOS women. This is a post hoc analysis of a single-center, double-blind RCT conducted between December 2011 and October 2017 at the endocrine outpatient clinic at the Medical University of Graz, Austria. We included 180 PCOS women and 150 non-PCOS women with serum 25-hydroxyvitamin D (25(OH)D) concentrations <75 nmol/L in the trial. We randomized subjects to receive 20,000 IU of VD3/week (119 PCOS, 99 non-PCOS women) or placebo (61 PCOS, 51 non-PCOS women) for 24 weeks. Outcome measures were AMH, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, dehydroepiandrosterone sulfate, and androstenedione. In PCOS women, we observed a significant treatment effect on FSH (mean treatment effect 0.94, 95% confidence interval [CI] 0.087 to 1.799, p = 0.031) and LH/FSH ratio (mean treatment effect -0.335, 95% CI -0.621 to 0.050, p = 0.022), whereas no significant effect was observed in non-PCOS women. In PCOS women, VD treatment for 24 weeks had a significant effect on FSH and LH/FSH ratio but no effect on AMH levels.

Vitamin D Concentrations at Term Do Not Differ in Newborns and Their Mothers with and without Polycystic Ovary Syndrome.

Studies suggest that non-pregnant women with polycystic ovary syndrome (PCOS) may be at elevated risk of 25 hydroxyvitamin D (25(OH)D) deficiency. Furthermore, there is evidence suggesting that 25(OH)D may also play an important role during pregnancy. Data regarding 25(OH)D deficiency during pregnancy in PCOS patients and its association with perinatal outcome is scarce. The aim of the study was to investigate whether mothers with and without PCOS have different 25(OH)D levels at term, how maternal 25(OH)D levels are reflected in their offspring, and if 25(OH)D levels are associated with an adverse perinatal outcome. Therefore, we performed a cross-sectional observational study and included 79 women with PCOS according to the ESHRE/ASRM 2003 definition and 354 women without PCOS and an ongoing pregnancy ≥ 37 + 0 weeks of gestation who gave birth in our institution between March 2013 and December 2015. Maternal serum and cord blood 25(OH)D levels were analyzed at the day of delivery. Maternal 25(OH)D levels did not differ significantly in women with PCOS and without PCOS (p = 0.998), nor did the 25(OH)D levels of their respective offspring (p = 0.692). 25(OH)D deficiency (<20 ng/mL) was found in 26.9% and 22.5% of women with and without PCOS (p = 0.430). There was a strong positive correlation between maternal and neonatal 25(OH)D levels in both investigated groups (r ≥ 0.79, p < 0.001). Linear regression estimates of cord blood 25(OH)D levels are about 77% of serum 25(OH)D concentrations of the mother. Compared to healthy controls, the risk for maternal complications was increased in PCOS women (48% vs. 65%; p = 0.009), while there was no significant difference in neonatal complications (22% and 22%; p = 1.0). However, 25(OH)D levels were similar between mothers and infants with and without perinatal complications. Although the share of women and infants with 25(OH)D deficiency was high in women with PCOS and without PCOS, it seems that the incidence of adverse perinatal outcome was not affected. The long-term consequences for mothers and infants with a 25(OH)D deficiency have to be investigated in future studies.

Effects of vitamin D supplementation on metabolic and endocrine parameters in healthy premenopausal women: A randomized controlled trial.

BACKGROUND & AIMS: Vitamin D supplementation may affect glycemic as well as hormonal regulation. Thus, the aim of the current study was to investigate whether vitamin D supplementation has any significant effects on metabolic and endocrine parameters in healthy premenopausal women. Primary outcome measure was the plasma glucose area under the curve (AUCgluc). METHODS: The current study was a single-center, double-blind, randomized placebo-controlled trial that was conducted at the Medical University of Graz, Austria, between March 2013 and October 2017. One-hundred and fifty healthy premenopausal women with 25-hydroxyvitamin D [25(OH)D] concentrations <75 nmol/L once weekly received either 20,000 IU of cholecalciferol or placebo (2:1 ratio) over a total of 24 weeks. RESULTS: In total, 127 women [age 36.2 ± 8.7 years; BMI 25.3 ± 5.6 kg/m2; baseline 25(OH)D 55.8 ± 19.7 nmol/L] completed the study. Vitamin D supplementation had no significant effect on AUCgluc (mean treatment effect 11.70; p = 0.069), while it had a significant treatment effect on homeostatic model assessment-insulin resistance (HOMA-IR; mean treatment effect 0.31; p = 0.019) and quantitative insulin-sensitivity check index (QUICKI; mean treatment effect -0.019; p = 0.013). There was no significant effect on the remaining secondary outcome parameters. CONCLUSIONS: In this randomized-controlled trial in healthy premenopausal women, there was a significant treatment effect of vitamin D supplementation on HOMA-IR and QUICKI, while there was no significant treatment effect on AUCgluc.

Androgen and Anti-Mullerian Hormone Concentrations at Term in Newborns and Their Mothers with and without Polycystic Ovary Syndrome.

Objectives: The aetiology of polycystic ovary syndrome (PCOS) is not particularly mapped; however, a complex interaction of various factors, such as genetic, environmental and intrauterine factors, can be assumed. Experimental animal studies and clinical observations support the hypothesis that developmental programming by excess intrauterine steroid is relevant. The aim of the study was to investigate whether mothers with and without PCOS exhibit different androgen and anti-Mullerian hormone (AMH) levels at the end of pregnancy and how maternal hormone levels are reflected in their offspring. Methods: Between March 2013 and December 2015, we performed a prospective cross-sectional study at the Medical University of Graz. We included 79 women with PCOS according to the ESHRE/ASRM 2003 definition and 354 women without PCOS, both with an ongoing pregnancy ≥37 + 0 weeks of gestation, who gave birth in our institution. Primary outcome parameters were the levels of maternal and neonatal androgens (testosterone, free testosterone, androstenedione) and AMH at delivery. Results: Androgen levels in female offspring of PCOS and non-PCOS women at birth did not differ, while maternal hormone levels differed significantly. Androgen levels in PCOS boys were significantly higher when compared to levels in PCOS girls. Discussion: Our findings do not support the hypothesis that maternal androgen excess contributes to elevated androgen concentrations in the female offspring. Nevertheless, the effects of the increased androgen concentrations in mothers on their offspring have to be investigated in future studies.

Effects of Vitamin D Supplementation on Body Composition and Metabolic Risk Factors in Men: A Randomized Controlled Trial.

Vitamin D might play a role in metabolic processes and obesity. We therefore examined vitamin D effects on metabolic markers and obesity in a randomized controlled trial (RCT). This is a post-hoc analysis of the Graz Vitamin D&TT-RCT, a single-center, double-blind, randomized placebo-controlled trial. We included 200 healthy men with serum 25-hydroxyvitamin D (25(OH) D) levels <75 nmol/L. Subjects received 20,000 IU of vitamin D3/week (n = 100) or placebo (n = 100) for 12 weeks. Outcome measures were metabolic markers, anthropometric measures, and body composition assessed by Dual-energy X-ray absorptiometry. One-hundred and ninety-two men completed the study. We found a significant treatment effect on fasting glucose/fasting insulin ratio (-5.3 (-10.4 to -0.2), p = 0.040), whereas we observed no significant effect on the remaining outcome parameters. In subgroup analyses of men with baseline 25(OH)D levels <50 nmol/L (n = 80), we found a significant effect on waist circumference (1.6 (0.3 to 2.9) cm, p = 0.012), waist-to-hip ratio (0.019 (0.002 to 0.036), p = 0.031), total body fat (0.029 (0.004 to 0.055) %, p = 0.026), and android fat (1.18 (0.11 to 2.26) %, p = 0.010). In middle-aged healthy men, vitamin D treatment had a negative effect on insulin sensitivity. In vitamin D deficient men, vitamin D has an unfavorable effect on central obesity and body composition.

Does third trimester cervical length predict duration of first stage of labor?

OBJECTIVE: To examine the association between third trimester cervical length (CL) measurement and duration of the first stage of labor. METHODS: This prospective cohort study included women with a singleton pregnancy who had routine CL measurements taken by transvaginal ultrasonography between 37 and 39 weeks gestation. Subjective duration of the first stage of labor was defined as the duration of contractions that the women subjectively had from the onset of regular contractions to full effacement of the cervix. Objective duration of first stage of labor was defined as 3 cm cervical dilation independent of cervical effacement until full effacement of the cervix. Associations between variables were analyzed using nonparametric correlations coefficients. A model relating the duration of labor to predictors was built using linear regression. RESULTS: In this analysis a total of 129 women were included. There was no significant correlation between CL and subjective duration of labor (ρ = -0.037, p = 0.695); however, a reduction in CL increased the objective duration of the first stage of labor (ρ = -0.269, p = 0.013). In univariate analysis parity (p = 0.018), hypertensive disorders (p = 0.013) and induction of labor (p = 0.022) were significantly associated with subjective duration of the first stage of labor. CONCLUSION: A long cervix in the third trimester is not associated with a prolonged first stage of labor. Induction of labor and multiparity were associated with a shorter first stage of labor while hypertension was associated with a longer duration of labor.

Effects of Vitamin D Supplementation on Bone Turnover and Bone Mineral Density in Healthy Men: A Post-Hoc Analysis of a Randomized Controlled Trial.

Vitamin D is well known for its effects on calcium and mineral metabolism. However, vitamin D effects on bone turnover markers (BTMs), which are used together with bone mineral density (BMD) to evaluate bone health, are less clear. We therefore examined vitamin D effects on BTMs (beta-cross laps (CTX) and osteocalcin (OC)) and BMD in a post-hoc analysis of a randomized controlled trial (RCT). This is a post-hoc analysis of the Graz Vitamin D&TT-RCT, a single-center, double-blind, randomized placebo-controlled trial conducted between December 2012 and November 2017 at the endocrine outpatient clinic at the Medical University of Graz, Austria. A total of 200 healthy men with serum 25-hydroxyvitamin D (25(OH)D) levels <75 nmol/L participated in the trial. Subjects were randomized to receive 20,000 IU of vitamin D3/week (n = 100) or placebo (n = 100) for 12 weeks. Outcome measures were BTMs, BMD, and trabecular bone score (TBS). A total of 192 men (mean age and 25(OH)D: 43 (±13) years and 54.9 (±18.3) nmol/L, respectively) completed the study. We found no significant treatment effect on BTMs, BMD, or TBS (p > 0.05 for all). In middle-aged healthy men, vitamin D treatment for 12 weeks had no significant effect on BTMs or BMD.

Effects of vitamin D supplementation on metabolic and endocrine parameters in PCOS: a randomized-controlled trial.

PURPOSE: Vitamin D status may be associated with insulin resistance and other key features of polycystic ovary syndrome (PCOS), but data from preliminary randomized controlled trials (RCTs) are conflicting. Therefore, we aimed to investigate the effects of vitamin D supplementation on plasma glucose area under the curve (AUCgluc, primary outcome measure) and on other metabolic and endocrine parameters (secondary outcome measures). METHODS: This study was a single-center, double-blind, randomized placebo-controlled trial conducted between December 2011 and July 2017 at the Medical University of Graz, Austria. One-hundred and eighty women with PCOS and 25-hydroxyvitamin D [25(OH)D] concentrations < 75 nmol/L were randomized in a 2:1 ratio to either receive 20,000 IU of cholecalciferol weekly or placebo over 24 weeks. Primary outcome was the between-group difference in AUCgluc at study end while adjusting for baseline values. RESULTS: In total, 123 participants completed the study [age 25.9 ± 4.7 years; BMI 27.5 ± 7.3 kg/m2; baseline 25(OH)D 48.8 ± 16.9 nmol/L, baseline fasting glucose 84 ± 8 mg/dL]. Vitamin D supplementation lead to a significant increase in 25(OH)D [mean treatment effect 33.4 nmol/L; 95% confidence interval (CI) 24.5 to 42.2; p < 0.001] but had no significant effect on AUCgluc (mean treatment effect - 9.19; 95% CI - 21.40 to 3.02; p = 0.139). Regarding secondary outcome measures, we observed a significant decrease in plasma glucose at 60 min during oral glucose tolerance test (mean treatment effect - 10.2 mg/dL; 95% CI - 20.2 to - 0.3; p = 0.045). CONCLUSIONS: Vitamin D supplementation had no significant effect on metabolic and endocrine parameters in PCOS with the exception of a reduced plasma glucose during OGTT.

Effects of vitamin D supplementation on androgens in men with low testosterone levels: a randomized controlled trial.

PURPOSE: It has been hypothesized that vitamin D is associated with androgen levels in men. We, therefore, aimed to evaluate whether vitamin D supplementation increases serum total testosterone (TT) levels in men with low TT levels at baseline. METHODS: The Graz Vitamin D&TT-RCT is a single-center, double-blind, randomized placebo-controlled trial conducted between March 2013 and November 2017 at the endocrine outpatient clinic at the Medical University of Graz, Austria. One-hundred healthy men with serum TT levels < 10.4 nmol/l and 25-hydroxyvitamin D [25(OH)D] levels < 75 nmol/l participated in the trial. Subjects were randomized to receive 20,000 IU of vitamin D3/week (n = 50) or placebo (n = 50) for 12 weeks. Primary outcome was TT measured using mass spectrometry. Secondary outcomes were free testosterone, free androgen index, sex hormone-binding globulin, estradiol, follicle-stimulating hormone, luteinizing hormone, metabolic characteristics, and body composition. RESULTS: Ninety-four men [mean age and 25(OH)D: 47 (± 12) years and 56.3 (± 18.3) nmol/l, respectively] completed the study. We found no significant treatment effect on serum TT or on the remaining secondary outcome variables. CONCLUSION: Vitamin D treatment had no effect on serum TT levels in middle-aged healthy men with low TT levels.

Early skin-to-skin contact after cesarean section: A randomized clinical pilot study.

OBJECTIVE: Early bonding by skin-to-skin contact (SSC) has been demonstrated to be beneficial for mothers and newborns following vaginal delivery. The aim of this study was to investigate the impact of intraoperative bonding (early SSC) after cesarean section on neonatal adaptation, maternal pain and stress response. STUDY DESIGN: This prospective, randomized-controlled pilot study was performed at a single academic tertiary hospital (Department of Obstetrics and Gynecology, Medical University of Graz, Austria) between September 2013 and January 2014. Women were randomly assigned to intraoperative ("early") SCC (n = 17) versus postoperative ("late") SCC (n = 18). Main variables investigated were neonatal transition (Apgar score, arterial oxygen saturation, heart rate and temperature), maternal pain perception and both maternal and neonatal stress response by measuring the stress biomarkers salivary free cortisol and salivary alpha amylase. RESULTS: There was no evidence for differences in parameters reflecting neonatal transition or stress response between the 'Early SSC Group' and the 'Late SSC Group'. Maternal salivary cortisol and alpha-amylase levels as well as maternal wellbeing and pain did not differ between the groups. However, the rise of maternal salivary alpha-amylase directly after delivery was higher in the 'Early SSC Group' compared to the 'Late SSC Group' (p = 0.004). CONCLUSIONS: This study did not reveal significant risks for the newborn in terms of neonatal transition when early SSC is applied in the operating room. Maternal condition and stress marker levels did not differ either, although the rise of maternal salivary alpha-amylase directly after delivery was higher in the 'Early SSC Group' compared to the 'Late SSC Group', which may indicate a stressor sign due to intensive activation of the sympathetic-adreno-medullary-system. This needs to be further evaluated in a larger prospective randomized trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT01894880.

Placenta praevia: incidence, risk factors and outcome.

OBJECTIVE: Aim of this study was to evaluate the incidence, potential risk factors and the respective outcomes of pregnancies with placenta praevia. METHODS: Data were prospectively collected from women diagnosed with placenta praevia in 10 Austrian hospitals in in the province of Styria between 1993 and 2012. We analyzed the incidence, potential risk factors and the respective outcomes of pregnancies with placenta praevia. Differences between women with major placenta praevia (complete or partial placenta praevia) and minor placenta praevia (marginal placenta praevia or low-lying placenta) were evaluated. RESULTS: 328 patients with placenta praevia were identified. The province wide incidence of placenta praevia was 0.15%. Maternal morbidity was high (ante-partum bleeding [42.3%], post-partum hemorrhage [7.1%], maternal anemia [30%], comorbid adherent placentation [4%], and hysterectomy [5.2%]) and neonatal complications were frequent (preterm birth [54.9%], low birth weight <2500 g [35.6%], Apgar-score after five minutes <7 [5.8%], and fetal mortality [1.5%]. Women with major placenta praevia had a significant higher incidence of preterm delivery, birthweight <2500 g and Apgar-score after five minutes <7. CONCLUSIONS: Placenta praevia was associated with adverse maternal (34.15%) and neonatal (60.06%) outcome. The extent of placenta praevia was not related with differences regarding risk factors and maternal outcome.

Prenatal management of monoamniotic twin pregnancies.

OBJECTIVE: To evaluate antenatal surveillance strategies and the optimal timing of delivery for monoamniotic twin pregnancies. METHODS: Obstetric and perinatal outcomes were retrospectively retrieved for 193 monoamniotic twin pregnancies. Fetal and neonatal outcomes were compared between fetuses followed in an inpatient setting and those undergoing intensive outpatient follow-up from 26 to 28 weeks of gestation until planned cesarean delivery between 32 and 35 weeks of gestation. The risk of fetal death was compared with the risk of neonatal complications. RESULTS: Fetal deaths occurred in 18.1% of fetuses (70/386). Two hundred ninety-five neonates from 153 pregnancies were born alive after 23 weeks of gestation. There were 17 neonatal deaths (5.8%), five of whom had major congenital anomalies. The prospective risk of a nonrespiratory neonatal complication was lower than the prospective risk of fetal death after 32 4/7 weeks of gestation (95% confidence interval 32 0/7-33 4/7). The incidence of death or a nonrespiratory neonatal complication was not significantly different between fetuses managed as outpatients (14/106 [13.2%]) or inpatients (15/142 [10.5%]; P=.55). Our statistical power to detect a difference in outcomes between these groups was low. CONCLUSIONS: The in utero risk of a monoamniotic twin fetus exceeds the risk of a postnatal nonrespiratory complication at 32 4/7 weeks of gestation. If close fetal surveillance is instituted after 26-28 weeks of gestation and delivery takes place at approximately 33 weeks of gestation, the risk of fetal or neonatal death is low, no matter the surveillance setting. LEVEL OF EVIDENCE: II.